Noncanonical inheritance of phenotypic information by protein amyloids.

Autor: Eroglu M; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. me2839@columbia.edu.; Developmental and Stem Cell Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada. me2839@columbia.edu., Zocher T; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.; Developmental and Stem Cell Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada., McAuley J; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.; Developmental and Stem Cell Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada., Webster R; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.; Developmental and Stem Cell Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada., Xiao MZX; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.; Developmental and Stem Cell Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada., Yu B; Developmental and Stem Cell Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada., Mok C; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada., Derry WB; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. brent.derry@sickkids.ca.; Developmental and Stem Cell Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada. brent.derry@sickkids.ca.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2024 Oct; Vol. 26 (10), pp. 1712-1724. Date of Electronic Publication: 2024 Sep 02.
DOI: 10.1038/s41556-024-01494-9
Abstrakt: All known heritable phenotypic information in animals is transmitted by direct inheritance of nucleic acids, their covalent modifications or histone modifications that modulate expression of associated genomic regions. Nonetheless, numerous familial traits and disorders cannot be attributed to known heritable molecular factors. Here we identify amyloid-like protein structures that are stably inherited in wild-type animals and influence traits. Their perturbation by genetic, environmental or pharmacological treatments leads to developmental phenotypes that can be epigenetically passed onto progeny. Injection of amyloids isolated from different phenotypic backgrounds into naive animals recapitulates the associated phenotype in offspring. Genetic and proteomic analyses reveal that the 26S proteasome and its conserved regulators maintain heritable amyloids across generations, which enables proper germ cell sex differentiation. We propose that inheritance of a proteinaceous epigenetic memory coordinates developmental timing and patterning with the environment to confer adaptive fitness.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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